There is growing interest in the generation of oxygen radicals and the role they may play in various biological pathways. Microsomes are capable of generating a variety of oxygen radicals. Hepatic microsomes oxidize ethanol to acetaldehyde in a NADPH-dependent, cytochrome P-450 mediated reaction. Ethanol affects the metabolism of a variety of common drugs. The mechanism responsible for microsomal oxidation of ethanol and its interaction with drugs has not been elucidated. Ethanol is a potent scavenger of hydroxyl radicals. The objective of this application is to study the generation of hydroxyl radicals by microsomal electron transfer and evaluate the possibility that the oxidation of ethanol by liver microsomes represents a system potentially dependent upon the interaction of ethanol with hydroxyl radicals. The effect of hydroxyl radical scavenging agents on microsomal oxidation of alcohols, drugs and on associated microsomal functions including the generation of hydroxyl radicals will be studied, using microsomes from control rats, and rats treated with inducers of microsomal functions e.g. phenobarbital, methylcholanthrene, ethanol. Experiments will also be carried out with purified cytochrome P-450 preparations. Studies on the mechanism by which microsomes and cytochrome P-450 generate hydroxyl radicals will be undertaken. These studies may determine, at the molecular level, the mechanism underlying the oxidation of ethnanol by liver microsomes. The information derived from these studies may also contribute basic knowledge to mechanisms of drug metabolism in control and induced peparations and further charaterize the role of oxygen radicals in biological pathways.